Novel broad spectrum virucidal molecules against enveloped viruses
157.37, 152.53, 135.17, 130.58,122.56, 115.74, 113.73, 112.82, 109.84, 52.40, 29.59; MS (ESI):
m/z 245.0 [M-H]-;
4-(5-Formylfuran-2-yl)-2-hydroxybenzoic acid (6). Compound 5 was dissolved in 25
mL of CH3OH, then a solution of NaOH 1M (5.00 mmol) was added dropwise, after the reac-
tion mixture was heated at reflux. The reaction mixture was stirred overnight until completion
(TLC). Organic solvent was removed under reduced pressure, then some water was added and
the aqueous layer was extracted three times with Et2O; the aqueous layer was then acidified to
pH 1 with HCl 6N and a precipitated appeared. (6) was obtained as a brown-red solid (yield:
95%); mp = 230˚C (decomposition); 1H NMR (DMSO, 400 MHz): ð = 9.63 (s, 1H), 7.88–7.86
(d, 1H, J = 8 Hz), 7.66–7.65 (d, 1H, J = 4 Hz), 7.45–7.39 (m, 3H); 13C NMR (DMSO, 100
MHz): ð = 178.72, 171.68, 161.69, 156.82, 152.63, 135.11, 131.72, 125.14, 116.02, 114.06,
113.29, 111.53; MS (ESI): m/z 231.0 [M-H]-;
General procedure for the synthesis of final compounds 9a-e. To a solution of bis(car-
boxymethyl)trithiocarbonate (0.22 mmol) in DME (1.0 mL) were added TEA (0.22 mmol) and
the opportune amine (0.22 mmol). The reaction mixture was heated at 90˚C for 10 min under
microwave irradiation. After this time, the aldehyde 6 (0.22 mmol) was added and the mixture
was heated at 110˚C for 5 min under microwave irradiation. The reaction mixture was evapo-
rated to dryness, then MeOH and a drop of HCl 2N were added; the final rhodanine deriva-
tives were obtained as a pure precipitate, isolated by filtration, washed with water and hexane,
and finally dried under high vacuum.
(Z)-4-(5-((3-(2-(1H-Indol-3-yl)ethyl)-4-oxo-2-thioxothiazolidin-5- ylidene)methyl)
furan-2-yl)-2-hydroxybenzoic acid (9a). (Yield: 55%); Yellow-brown solid; mp = 254˚C
(decomposition); 1 H NMR: ((CD3)2CO, 400 MHz) δ = 8.00–7.98 (d, 1H, J = 8.4 Hz), 7.76–
7.74 (d, 1H, J = 8 Hz), 7.64 (s, 1H), 7.47–7.33 (m, 5H), 7.22 (s, 1H), 7.11–7.02 (m, 2H) 4.41–
4.37 (m, 2H), 3.19–3.15 (m, 2H); 13C NMR (DMSO, 100 MHz): δ = 194.15, 171.77, 166.77,
161.81, 156.64, 150.49, 136.64, 134.91, 131.77, 127.45, 123.59, 123.10, 121.47, 120.25, 118.86,
118.53, 118.33, 115.53, 113.52, 113.09, 112.40, 111.90, 110.38, 45.23, 22.82; MS (ESI): m/z
489.0 [M-H]-;
(Z)-4-(5-((3-(4-bromophenethyl)-4-oxo-2-thio-oxothiazolidin-5-ylidene)methyl)furan-
2-yl)-2-hydroxybenzoic acid (9b). (Yield: 89%); Brown solid. Mp = 275˚C (decomposition);
1H NMR: (DMSO, 400 MHz) δ = 7.93–7.91 (d, 1H, J = 8.4 Hz), 7.64 (s, 1H), 7.48–7.46 (m,
3H), 7.39–7.36 (m, 3H), 7.18–7.16 (m, 2H), 4.24–4.21 (m, 2H), 2.96–2.93 (m, 2H) ppm. 13
C
NMR (DMSO, 100 MHz): δ = 194.07, 171.54, 166.68, 161.86, 156.87, 150.49, 137.55, 134.85,
131.72, 131.50, 131.34, 123.05, 120.02, 119.43, 118.48, 115.51, 114.05, 112.90, 112.53, 45.32,
31.96 ppm. MS (ESI): m/z 529.0 [M-H]-. Purity: 97.5%.
(Z)-2-hydroxy-4-(5-((3-(4-methoxyphenethyl)-4-oxo-2-thioxothiazolidin-5-ylidene)
methyl)furan-2-yl)benzoic acid (9c). (Yield: 79%); Yellow solid. Mp = 265˚C (decomposi-
tion); 1H NMR: (DMSO, 400 MHz) δ = 7.90–7.88 (d, 1H, J = 8.0 Hz), 7.60 (s, 1H), 7.45–7.44
(d, 1H, J = 3.6 Hz), 7.36–7.33 (m, 3H), 7.13–7.10 (d, 2H, J = 8.4 Hz), 6.85–6.83 (d, 2H, J = 8.4
Hz), 4.18–4.14 (m, 2H), 3.70 (s, 3H), 2.89–2.85 (m, 2H) ppm. 13C NMR (DMSO, 100 MHz): δ
= 193.99, 171.74, 166.65, 161.81, 158.40, 156.68, 150.46, 134.89, 131.76, 130.05, 129.82, 123.13,
120.00, 118.39, 115.53, 114.33, 113.60, 113.06, 112.42, 55.37, 45.85, 31.67 ppm. MS (ESI): m/z
481.0 [M-H]-. HPLC: purity: 98.5%.
(Z)-2-hydroxy-4-(5-((3-(4-isopropylphenethyl)-4-oxo-2-thioxothiazolidin-5-ylidene)
methyl)furan-2-yl)benzoic acid (9d). (Yield: 87%); Orange solid. Mp = 259˚C (decomposi-
tion); 1H NMR: (DMSO, 400 MHz) δ = 7.89–7.87 (d, 1H, J = 8.0 Hz), 7.59 (s, 1H), 7.43–7.40
(m, 2H), 7.34–7.31 (m, 2H), 7.15–7.12 (m, 4H), 4.18–4.14 (m, 2H), 2.89–2.85 (m, 2H), 1.39 (s,
1H), 1.17–1.15 (m, 6H) ppm. 13C NMR (DMSO, 100 MHz): δ = 193.97, 171.77, 166.62, 161.83,
156.69, 150.45, 147.10, 135.29, 134.86, 131.72, 128.91, 126.83, 125.16, 123.13, 120.02, 118.36,
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